Cangrelor Provides Effective Maintenance of Platelet Inhibition

Thienopyridines are anti-platelet medications that work to prevent blood clotting and improve circulation. Though they are among the most widely prescribed medications, their use can be complicated by the unanticipated need for surgery. Despite increased risk of thrombosis, guidelines recommend discontinuing thienopyridines 5 – 7 days prior to surgery to minimise bleeding.

BRIDGE is a prospective, randomised double-blind, placebo-controlled, multicenter trial in 210 patients with acute coronary syndrome (ACS) or treated with a coronary stent on a thienopyridine awaiting coronary artery bypass grafting (CABG) to receive either cangrelor or placebo after an initial open-label, dose-finding phase. After thienopyridines were stopped, patients were administered cangrelor or a placebo for at least 48 hours, which was then discontinued 1 – 6 hours prior to surgery.

The primary efficacy endpoint of the trial was platelet reactivity (measured in P2Y12 Reaction Units [PRU]), assessed daily with the VerifyNowTM P2Y12 assay. The main safety endpoint was excessive CABG-related bleeding.

The dose of cangrelor determined in the open-label stage was 0.75 µg/kg/min. In the randomised phase, a greater proportion of patients treated with cangrelor had low levels of platelet reactivity throughout the entire treatment period compared with placebo (primary endpoint, PRU<240: 98.8 per cent vs. 19.0 per cent; odds ratio: 353, 95 per cent confidence interval: 45.6-2728, p<0.001). Excessive CABG-related bleeding occurred in 11.8 per cent vs. 10.4 per cent in the cangrelor and placebo groups, respectively (p=0.76). There were no significant differences in major bleeding prior to CABG, although minor bleeding was numerically higher with cangrelor.

"Results of the BRIDGE trial indicate that in patients on thienopyridines who undergo cardiac surgery, intravenous cangrelor provides effective maintenance of platelet inhibition with no apparent increase in major bleeding, despite numerically higher rates of minor bleeding prior to surgery, which however were mostly attributed to ecchymosis at the site of venipuncture. Larger patient samples are needed to more definitively assert the safety and effectiveness of cangrelor bridging therapy to surgery," said Doctor Dominick J. Angiolillo of the University of Florida College of Medicine in Jacksonville, Florida.